Spontaneous minute ventilation is a predictor of extubation failure in extremely-low-birth-weight infants.

OBJECTIVE: To validate the percentage of time spent below a target value of spontaneous expiratory minute ventilation (< 125 ml/min per kg) during a 2-h period of continuous positive airway pressure (CPAP) via an endotracheal tube (ETT) as a predictor of failed extubation in preterm infants. METHODS: Forty-one infants intubated for at least 24 h, with birth weight between 500 and 1000 g, who were clinically stable and at ventilator setting compatible with an extubation attempt, were studied during a 2-h period of ETT CPAP. Dynamic lung compliance and total lung resistance were measured during a period of quiet breathing, while tidal volume (Vt), respiratory rate and the corresponding spontaneous expiratory minute ventilation values were calculated for the complete recording period of 2 h using a customized computer program. The time each patient spent below the target spontaneous expiratory minute ventilation value was reported as a percentage of the total recorded time (% spontaneous expiratory minute ventilation < 125 ml/min per kg). Extubation failure was defined as the need for reintubation within 72 h. RESULTS: Eleven out of 41 babies (26.8%) experienced failure of extubation (failure group) while 30 infants (73.2%) were successfully extubated (success group). There were no significant differences in dynamic lung compliance and lung resistance between the two groups, but the mean values of respiratory rate and spontaneous expiratory minute ventilation were significantly lower in the failure group than in the success group: 43 (37-56) breaths/min and 240 (160-353) ml/min per kg vs. 53 (28-67) breaths/min and 309 (223-434) ml/min per kg, respectively (p = 0.0129 and p = 0.0039). Moreover, the babies in whom extubation failed spent a longer time below the target value of spontaneous expiratory minute ventilation when compared with successfully extubated babies (p < 0.0001). Percentage of time spent with spontaneous expiratory minute ventilation < 125 ml/min per kg had a larger area than transcutaneous (Tc)PCO2, TcPO2 and pulse oxymetry saturation (SpO2) under the receiver operator characteristic curves. CONCLUSION: The measurement of spontaneous expiratory minute ventilation prior to extubation could be useful in identifying those babies who are not ready for spontaneous ventilation.     

Effect on growth of two different dexamethasone courses for preterm infants at risk of chronic lung disease. A randomized trial.

A randomized study was designed to evaluate the effects of two different dexamethasone courses on the growth of preterm infants. The first phase included 30 preterm infants at high risk for chronic lung disease (CLD). 15 babies (moderately early dexamethasone group) were treated with dexamethasone for 14 days, from the 10th day of life, and received a total dose of 4.75 mg/kg; 15 babies were assigned to the control group. The second phase included 30 preterm infants at high risk for CLD. 15 babies (early dexamethasone group) were treated with dexamethasone for 7 days, from the 4th day of life, and received a total dose of 2.38 mg/kg; 15 babies were assigned to the control group. All the main clinical baseline characteristics were similar between the groups both in the first and in the second phase. Infants given the two dexamethasone courses showed significantly reduced weight gain during the period of treatment when compared to the respective control group, but they had a weight catch-up soon after the end of treatment. At 30 days of life the weight and length gain of each treated group were similar to those of control infants, but the moderately early dexamethasone group showed a significantly poorer head growth. No differences between the groups were observed at discharge. Dexamethasone treatment induces a slower weight gain which is time-limited to the period of treatment and is followed by a body weight catch-up. However, the poorer head growth detected at 30 days of life in the infants who received a higher dose of dexamethasone could indicate important adverse effects, possibly dose-related, on postnatal brain growth and development.     

Delivery room strategies and outcomes in preterm infants with gestational age 24-28 weeks.

OBJECTIVE: To investigate the effect of different delivery room strategies on survival, short term morbidity, and outcomes in extremely premature infants. METHODS: This retrospective cohort study included all preterm infants with a gestational age between 24 and 28 weeks who were born in 1992-1997 (period A; n = 161) and in 1998-2003 (period B; n = 163). In period A, elective intubation was performed. In period B, if spontaneous breathing was present, nasal continuous positive airway pressure (nCPAP) was applied. RESULTS: Survival rate and the number of never-intubated infants significantly increased in period B. No differences were found concerning short-term morbidity. Among major outcomes, the need for retinopathy of prematurity (ROP) surgery and the length of stay were significantly lower in period B. Subgroup analysis showed no significant differences from period A to period B in infants with gestational age 24-26 weeks. In the 27-28 weeks subgroup, the never-intubated infants rate increased from 2.8% to 21.3% and survival rate increased from 63% to 79%. A reduced need for ROP surgery and a shorter hospital stay were also observed. CONCLUSIONS: Changes in delivery room strategy tending to reduce mechanical ventilation in extremely premature infants are likely to benefit essentially infants of 27-28 weeks of gestation. Extension of such benefits to premature infants at the limit of viability requires further research.     

Human alloantigen-specific anergic cells induced by a combination of CTLA4-Ig and CsA maintain anti-leukemia and anti-viral cytotoxic responses

The success of allogeneic hematopoietic stem cell transplantation from HLA-disparate donors depends on the development of new strategies for graft-versus-host disease prevention able to target specifically donor antihost alloreactivity, while preserving GVL and antiviral immune surveillance. Recent experimental and clinical work has shown the feasibility of an approach based on induction of anergy to host alloantigens through blockade of B7/CD28 costimulatory signal in donor T cells, but data on the impact of this strategy on the recovery of the immune system are still lacking. We devised an ex vivo method for induction of host alloantigen-specific unresponsiveness based on treatment with the B7/CD28 blocking agent CTLA4-Ig associated with CsA. We then proceeded to assess the maintenance of an effective immune response towards viral pathogens and tumor cells after CTLA4-Ig/CsA treatment, by measuring the frequency of CTL precursors directed against CMV- and EBV-infected targets, and against autologous leukemic blasts. We demonstrated that (1) CTLA4-Ig and CsA can act synergistically in inducing a state of unresponsiveness to alloantigens; (2) the number of leukemia-reactive, EBV-specific and CMV-specific CTLp is not impaired by CTLA4-Ig/CsA treatment. Our data provide the first direct in vitro evidence that it is possible to preserve antiviral and antileukemia effector cells after blockade of CD28/B7 interaction during MLR.     

Rehabilitation of chronic graft versus host disease in children. A clinical series

The study was aimed at evaluating clinical and functional assessment and results obtained following rehabilitative treatment in children affected by chronic graft versus host disease (cGVHD) after allogeneic transplantation of hemopoietic stem cells (HSCT). From 1999 to 2003 we evaluated 6 children with cGVHD after HSCT presenting severe complications and disabilities. Clinical and functional assessment was performed prior to rehabilitative treatment (T1), at follow-up at 6 (T6) and 12 (T12) months after treatment. Each child received a personalized rehabilitative treatment program based on the use of neuromotor re-education techniques, massotherapy, chest rehabilitation and occupational therapy. Six children presented sclerodermoid skin lesions, joint contractures, anchylosis, respiratory insufficiency, postural and walking alterations which led to reduction in motor performance and autonomy in daily living activity. After 1 year of rehabilitation treatment, 3 patients showed improvement in motor performance, 2 remained stable and 1 patient worsened. Rehabilitative treatment associated with pharmacological therapy has proven to be useful in patients affected by cGVHD. We believe that cGVHD is a pathology which must be seen by a physiatrist as early as possible at onset of first cutaneous signs of cGVHD to limit its invalidating evolution.     

Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only proven curative therapy for juvenile myelomonocytic leukemia (JMML). We, the European Working Group on Childhood MDS (EWOG-MDS) and the European Blood and Marrow Transplantation (EBMT) Group, report the outcome of 100 children (67 boys and 33 girls) with JMML given unmanipulated HSCT after a preparative regimen including busulfan, cyclophosphamide, and melphalan. Forty-eight and 52 children received transplants from an HLA-identical relative or an unrelated donor (UD), respectively. The source of hematopoietic stem cells was bone marrow, peripheral blood, and cord blood in 79, 14, and 7 children, respectively. Splenectomy had been performed before HSCT in 24 children. The 5-year cumulative incidence of transplantation-related mortality and leukemia recurrence was 13% and 35%, respectively. Age older than 4 years predicted an increased risk of disease recurrence. The 5-year probability of event-free survival for children given HSCT from either a relative or a UD was 55% and 49%, respectively (P = NS), with median observation time of patients alive being 40 months (range, 6 to 144). In multivariate analysis, age older than 4 years and female sex predicted poorer outcome. Results of this study compare favorably with previously published reports. Disease recurrence remains the major cause of treatment failure. Outcome of UD-HSCT recipients is comparable to that of children receiving transplants from an HLA-identical sibling. (Blood. 2005;105:410-419)      

Rituximab for the treatment of refractory autoimmune hemolytic anemia in children

Autoimmune hemolytic anemia (AIHA) in children is sometimes characterized by a severe course, requiring prolonged administration of immunosuppressive therapy. Rituximab is able to cause selective in vivo destruction of B lymphocytes, with abrogation of antibody production. In a prospective study, we have evaluated the use of rituximab for the treatment of AIHA resistant to conventional treatment. Fifteen children with AIHA were given rituximab, 375 mg/m(2)/dose for a median of 3 weekly doses. All patients had previously received 2 or more courses of immunosuppressive therapy; 2 patients had undergone splenectomy. After completing treatment, all children received intravenous immunoglobulin for 6 months. Treatment was well tolerated. With a median follow-up of 13 months, 13 patients (87%) responded, whereas 2 patients did not show any improvement. Median hemoglobin levels increased from 7.7 g/dL to a 2-month posttreatment level of 11.8 g/dL (P <.001). Median absolute reticulocyte counts decreased from 236 to 109 x 10(9)/L (P <.01). An increase in platelet count was observed in patients with concomitant thrombocytopenia (Evans syndrome). Three responder patients had relapse, 7, 8, and 10 months after rituximab infusion, respectively. All 3 children received a second course of rituximab, again achieving disease remission. Our data indicate that rituximab is both safe and effective in reducing or even abolishing hemolysis in children with AIHA and that a sustained response can be achieved in the majority of cases. Disease may recur, but a second treatment course may be successful in controlling the disease.     

Comparison of horse and rabbit antithymocyte globulin in immunosuppressive therapy for refractory cytopenia of childhood

Refractory cytopenia of childhood is the most common subtype of myelodysplastic syndrome in children. In this study, we compared the outcome of immunosuppressive therapy using horse antithymocyte globulin (n=46) with that using rabbit antithymocyte globulin (n=49) in 95 patients with refractory cytopenia of childhood and hypocellular bone marrow. The response rate at 6 months was 74% for horse antithymocyte globulin and 53% for rabbit antithymocyte globulin (P=0.04). The inferior response in the rabbit antithymocyte globulin group resulted in lower 4-year transplantation-free (69% versus 46%; P=0.003) and failure-free (58% versus 48%; P=0.04) survival rates in this group compared with those in the horse antithymocyte globulin group. However, because of successful second-line hematopoietic stem cell transplantation, overall survival was comparable between groups (91% versus 85%; P=ns). The cumulative incidence of relapse (15% versus 9%; P=ns) and clonal evolution (12% versus 4%; P=ns) at 4 years was comparable between groups. Our results suggest that the outcome of immunosuppressive therapy with rabbit antithymocyte globulin is inferior to that of horse antithymocyte globulin. Although immunosuppressive therapy is an effective therapy in selected patients with refractory cytopenia of childhood, the long-term risk of relapse or clonal evolution remains. (ClinicalTrial.gov identifiers: {"type":"clinical-trial","attrs":{"text":"NCT00662090","term_id":"NCT00662090"}}NCT00662090)